Article pubs.acs.org/joc

Metal-Free Synthesis of Oxindoles via (NH4)2S2O8‑Mediated Halocarbocyclization of Alkenes in Water Ming-Zhong Zhang,† Wen-Bing Sheng,†,‡ Qing Jiang,† Mi Tian,† Yong Yin,† and Can-Cheng Guo*,† †

State Key Laboratory of Chemo/Biosensing and Chemometrics, Advanced Catalytic Engineering Research Center of the Ministry of Education, College of Chemistry and Chemical Engineering, Hunan University, Changsha 410082, China ‡ College of Pharmacy, Hunan University of Chinese Medicine, Changsha 410208, China S Supporting Information *

ABSTRACT: A metal-free synthesis of oxindoles was achieved through the (NH4)2S2O8-mediated halocarbocyclization of alkenes. This protocol provides a practical and environmentally benign method for the construction of halo-containing oxindoles in water. The advantages of this reaction are its good functional group tolerance and mild reaction conditions. On the basis of experimental observations, a plausible reaction mechanism is proposed.

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INTRODUCTION Oxindole constitutes the central core of a wide variety of naturally occuring and pharmaceutical molecules1 that exhibit potential biological activities (e.g., anti-inflammatory, anticancer, and Plasmodium falciparum-inhibitory activities).2 Among the known strategies for obtaining an oxindole framework, transition-metal-catalyzed oxidative C−H functionalization/ carbocyclization and direct oxidative C−H functionalization/ cyclization of alkenes are the most popular methods,3 particularly because these efficient approaches feature an easy availability of starting materials and excellent functional group compatibility. Additionally, visible-light-mediated radical C−H functionalization of alkenes provides a more direct and potentially more attractive strategy for the syntheses of oxindoles.4 However, all of these approaches have some limitations, including low atom efficiency and the high cost of photocatalysts, which greatly restrict their application in synthesis chemistry. Therefore, a straightforward and highly efficient method is still required. Recently, the introduction of heteroatomic groups was shown to induce the cyclization of alkenes, involving the simultaneous formation of C(sp3)−X (X = O, N, P, S, halogen, etc.) and C(sp2)−C(sp3) bonds, thus arising as a highly attractive strategy for creating oxindoles.5−10 For example, Zhu’s group first documented a palladium-catalyzed carboheterofunctionalization of alkenes to form oxindoles and spirooxindoles.5 The radical azidoarylation,6 arylphosphorylation,7 arylsulfonylation,8 ayltrifluoromethylthiolation,9 and aryltrifluoromethylation10 of arylacrylamides have been reported subsequently by other groups. Despite these advances, examples of the halocarbocyclization of alkenes are quite rare.11 In 2011, Zhu and coworkers realized the iodocarbocyclization of alkenes using PhI(OAc)2/I2 to afford 3,3′-disubstituted oxindoles (Scheme 1a).11a Gulder’s group also realized bromocarbocyclization by treating N-arylacrylamides with NBS/NH4Cl or KBr/oxone in the presence of a catalyst © XXXX American Chemical Society

Scheme 1. Halocarbocyclization of Alkenes

(Scheme 1b).11b To the best of our knowledge, however, there have been no reported examples concerning the chlorocarbocyclization of alkenes to access chloro oxindoles. In this regard, it is important to seek a practical and efficient method to broaden this area. Very recently, from economical and environmental points of view, establishing a green and sustainable approach to Received: July 30, 2014

A

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oxindole synthesis has attracted increasing attention.12 In this context, many metal-free conditions have been successfully developed.13 However, the use of water as the reaction medium for the C−H functionalization/cyclization of alkenes, especially without the addition of any organic cosolvents, is still a challenge.8a,14 All of these pioneering studies encouraged us to explore a novel and environmentally friendly system for halocarbocyclization reactions to access halo-substituted oxindoles. Herein, we report the novel (NH4)2S2O8-mediated halocarbocyclization of alkenes using NH 4 X (X = Cl, Br, I) as the halide source. It worth noting that this metal-free approach employs H2O as a solvent and successfully provides a versatile method for obtaining a wide range of halogenated oxindoles (Scheme 1c).

desired product 2a was observed (Table 1, entry 9). To our delight, 2a was produced as a single product in 65% yield after prolonging the reaction time to 48 h (Table 1, entry 10). It is worth noting that the reaction resulted in the production of 2a in nearly the same yield under an air or N2 atmosphere, thereby excluding the influence of air on this conversion (Table 1, entry 10 vs entry 11). We found that neither increasing the amount of NH4Cl nor using KCl as a chlorine source improved the reaction efficiency drastically; in fact, a trace amount of 3 was detected in these reactions (Table 1, entries 12 and 13). Subsequently, other oxidants, such as O2 (balloon) and PhI(OAc)2, were tested, but they were found to be less efficient than (NH4)2S2O8 (Table 1, entries 14 and 15). In addition, we investigated the solubility of starting material N-arylacrylamide 1a and product 2a in water. It was shown that in the (NH4)2S2O8/NH4Cl/H2O reaction system, 1.0 mL of solvent is capable of hosting a large amount of 2a (up to 0.32 mmol; for details, see Table S1); the reason was not very clear at this stage because very complicated concerted mechanisms might be involved during the solvation process. With the optimized conditions in hand, we next set out to explore the substrate scope and the limitations of the chlorocarbocyclization reaction (Table 2). The effect of various substitution patterns on the N-aryl moiety was first investigated. Unsurprisingly, the substrates with chloro substituents at the para and ortho positions of the N-aryl moiety resulted in moderate to good yields of product 2a. Other halo substitutions such as F, Br, and I groups on the N-aryl moiety were also tolerated, providing the corresponding oxindoles in 43−69% yields (products 2b−2d). Gratifyingly, strong electron-withdrawing substituents, such as a CN group, on the N-aryl moiety resulted in a moderate yield of product 2e, whereas electron-donating groups, such as a methyl group, were also tolerated on the aryl ring (product 2f). To our delight, the amide at which the N-methyl substituent is replaced by an ethyl group was also viable for the reaction. As expected,

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RESULTS AND DISCUSSION We initiated our studies by screening for the optimal conditions for the chlorocarbocyclization of N-arylacrylamide 1a. It was found that when the reaction was carried out in the presence of (NH4)2S2O8 (3.0 equiv) and NH4Cl (3.0 equiv) in H2O at 60 °C for 24 h, cyclized product 3 was produced in 40% yield (Table 1, entry 1). In the absence of (NH4)2S2O8, no reaction occurred, highlighting the importance of the oxidant (Table 1, entry 2). Changing the solvent to H2O−CH3CN or H2O−DCE afforded only a trace amount of 3 (Table 1, entries 3 and 4). It is worth noting that in this case aromatic C5- and C7-chloro-substituted oxindole 2a was also obtained in 10% yield (Table 1, entry 3). No further improvement was seen at higher temperature (80 °C, Table 1, entry 5), whereas increasing the amount of (NH4)2S2O8 increased the yield of 2a (Table 1, entries 6 and 7). Encouraged by these results, we expected to obtain 2a as a single product in a controllable manner. Unfortunately, a combination of K2S2O8 with KCl in H2O furnished only 3 in 37% yield (Table 1, entry 8). Even after the addition of phase-transfer catalysts such as 18-crown-6 (10 mol %) and TBACl (10 mol %), no amount of Table 1. Optimization of Reaction Conditionsa

yield (%)b entry

oxidant (equiv)

chlorine source (equiv)

solvent

time (h)

2a

3

1 2 3c 4d 5e 6 7 8 9f,g 10 11h 12 13 14 15

(NH4)2S2O8 (3.0)

NH4Cl (3.0) NH4Cl (3.0) NH4Cl (3.0) NH4Cl (3.0) NH4Cl (3.0) NH4Cl (3.0) NH4Cl (3.0) KCl (3.0) KCl (3.0) NH4Cl (3.0) NH4Cl (3.0) NH4Cl (4.0) KCl (3.0) NH4Cl (3.0) NH4Cl (3.0)

H2O H2O H2O−CH3CN H2O−DCE H2O H2O H2O H2O H2O H2O H2O H2O H2O H2O H2O

24 24 24 24 24 24 24 24 24 48 48 48 48 48 48

0 0 10 trace 12 23 30 0 0 65 64 68 61 0 41

40 0 trace trace trace 0 0 37 19 0 0 trace trace 0 25

(NH4)2S2O8 (3.0) (NH4)2S2O8 (3.0) (NH4)2S2O8 (3.0) (NH4)2S2O8 (5.0) (NH4)2S2O8 (6.0) K2S2O8 (3.0) K2S2O8 (6.0) (NH4)2S2O8 (6.0) (NH4)2S2O8 (6.0) (NH4)2S2O8 (6.0) (NH4)2S2O8 (6.0) O2 (balloon) PhI(OAc)2 (3.0)

Reaction conditions: 1a (0.2 mmol), solvent (1.0 mL), 60 °C. bYield of isolated product. cH2O−CH3CN (v−v, 1:1). dH2O−DCE (v−v, 1:1). Temperature = 80 °C. f18-crown-6 = 10 mol %. gTBACl = 10 mol %. hUnder a N2 atmosphere.

a e

B

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Table 2. Scope of the Chlorocarbocyclization Reactiona,b

Reaction conditions: 1 (0.2 mmol), (NH4)2S2O8 (1.2 mmol), NH4Cl (0.6 mmol), and H2O (1.0 mL) at 60 °C for 48 h. bYield of isolated product. Reaction time = 24 h. dDetermined by 1H NMR.

a c

substrates bearing m-methyl substituents afforded mixtures of two regioselective products (2g/2g′ in a ratio of 1:2.3). In addition, a tetrahydroquinoline derivative was also viable as a substrate to furnish tricyclic oxindole 2h in good yield, whereas an N-hydrogen atom-substituted amide resulted in no conversion (product 2i). Next, the substituent effect at the R3 position was investigated; a CH2OH substituent was well tolerated in this reaction (product 2j). Notably, 2-(methyl(phenyl)carbamoyl)allyl acetate was also a suitable substrate, albeit with a relatively low conversion and yield (product 2k). It was noted that substrates bearing a methyl group at the terminal alkene provided product 2l as a mixture of diastereoisomers (61%, >20:1 d.r.). Encouraged by these good results, we next set out to expand the application of such a reaction system to bromo- and iodocarbocyclization reactions. Much to our surprise, after optimization of the reaction conditions, the reaction of N-arylacrylamide 1a gave desired oxindoles 2m and 2r in good to high yields by using (NH4)2S2O8 (2.5 equiv) and NH4X (X = Br, I; 2.5 equiv) in H2O (1.0 mL) at 60 °C (Table 3). The effect of substituent groups on the N-aryl moiety was subsequently examined. Screening showed that both

electron-withdrawing and -donating substituents, such as Cl, I, MeO, and Me groups, were well tolerated under the optimal conditions. For instance, substrates bearing Cl and I groups at the para position of the N-aryl moiety provided corresponding bromo and iodo oxindoles in moderate to good yields. It is worth noting that the bromocarbocyclization of para-substituted substrates furnished aromatic ring bromo-substituted oxindoles (products 2n−2p). As for iodocarbocyclization, additional iodination of the phenyl ring was not observed (products 2r−2t). Notably, a meta-methyl-substituted substrate gave a mixture of two regioselective products 2q/2q′ and 2u/2u′ in ratios of 1.1:1 and 2:1, respectively. We were delighted to discover that pure 2q and 2u could be isolated by recrystallization from ethyl acetate/ petroleum ether in 29 and 45% yields, respectively. The fact that a meta-methyl-substituted substrate furnished phenyl ring iodo-substituted oxindoles is worth noting. In comparison, the para-methoxy-substituted substrate failed to give a phenyl ringiodinated product, presumably because of the directing effect of the substituted amino group that caused other positions on the aromatic ring to be less reactive than the C5 position as well as the weak eletrophilicity of the I+ species. C

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Table 3. Scope of the Bromo- and Iodocarbocyclizationa,b

a Reaction conditions: 1 (0.2 mmol), (NH4)2S2O8 (0.5 mmol), NH4X (X = Br, I) (0.5 mmol) and H2O (1.0 mL) at 60 °C for 24 h. bYield of isolated product. cYield of 2q after recrystallization. dReaction time = 48 h. eYield of 2u after recrystallization.

To demonstrate the viability of this procedure, we carried out the chlorocarbocyclization of two substrates on a large scale. The reaction of 0.88 g (5 mmol) of N-arylacrylamide 1a in the presence of 6.0 equiv of (NH4)2S2O8 and 3.0 equiv of NH4Cl in water gave 2a (0.81 g) in 58% isolated yield (eq 1). Additionally, the reaction of tetrahydroquinoline derivative 1h according to the same procedure successfully yielded desired tricyclic oxindole 2h (0.95 g) in 70% yield (eq 2).

These results suggest that a radical mechanism for this chlorocarbocyclization is unlikely. Second, when monochloro product 3 was reacted under the standard reaction conditions, 2a was isolated in high yield (Scheme 2c). The data indicated that the cyclization of 1a is probably the first step in this transformation. Third, the change in the color of the reaction mixture indicates the formation of molecular halogen during the reaction (Figure S1).16 In this transformation, a chlorinating agent was a key issue in investigating whether HClO or Cl2 was the activated chloride species, and verification experiments were performed. The treatment of 1a in 3.0 equiv of HOCl at room temperature in the dark smoothly provided 2a in 51% yield, but when the same reaction was carried out at 60 °C, 30% of product 2a was also obtained. The combination of Cl2 and H2O markedly increased the yield of 2a, whereas interestingly, the replacement of water with 1,2-dichloroethane under otherwise identical reaction conditions gave poor reactivity (7%, Scheme 2d). These results indicated that HOCl is presumably the real chlorinating agent in our reaction system. Finally, we envisioned that hydroxychlorination or dichlorination of an olefin may occur when the cyclization sites are blocked by other substituents. To prove this hypothesis, we synthesized a 2,6-disubstituted substrate (4) and subjected it to the standard reaction conditions, obtaining a mixture of dichlorinated and hydroxychlorinated products (5 and 6, respectively) in 45% yield (Scheme 2e). This is powerful proof that the reaction proceed via an electrophilic mechanism.

To gain insight into the reaction mechanism, we next gathered some additional information. First, under dark conditions or in the presence of radical scavengers such as 2,6-di-tert-butyl-4methylphenol (BHT) and 2,2,6,6-tetramethyl-1-piperidinyloxy (TEMPO), the transformation retains its reactivity (Scheme 2a,b).15 D

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Scheme 2. Control Experiments

Scheme 3. Possible Mechanism

On the basis of these results as well as related reports,17 a plausible mechanism is proposed in Scheme 3. Initially, the oxidation of the chlorine ion with persulfate ion generates molecular chlorine in situ, which is further transformed in water into HOCl and HCl. The reduced chlorine ion is reoxidized again by a persulfate ion to form molecular chlorine that becomes involved in the next reaction cycle. Subsequent electrophilic addition of HOCl in the form of a chlorinium ion (Cl+) at the double bond in 1a affords a three-membered cyclic chlorinum cation intermediate (A).17a Intramolecular nucleophilic attack of intermediate A with an aryl ring gives rise to cyclization intermediate B, followed by proton loss (H+) to afford intermediate 3. Finally,

electrophilic substitutions on the phenyl ring in intermediate 3 by a chlorinium ion (Cl+) take place to furnish desired product 2a.17b,c However, in our reaction system, the possibility of a related electrophilic mechanism via dichlorine monoxide (Cl2O)17c cannot be completely ruled out at present.

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CONCLUSIONS We have successfully developed a new and metal-free synthesis method for the oxidative halocarbocyclization of alkenes. This transformation provides a versatile and green method for the construction of halogenated oxindoles. Most importantly, the use of NH4X (X = Cl, Br, I) as the halide source, (NH4)2S2O8 E

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solid in 65% yield (36.2 mg); flash chromatography (petroleum ether/ ethyl acetate, 8:1); mp 58−59 °C; 1H NMR (400 MHz, CDCl3) δ 7.27 (d, J = 2.0 Hz, 1H), 7.17 (d, J = 2.0 Hz, 1H), 3.79 (d, J = 10.9 Hz, 1H), 3.70 (d, J = 10.9 Hz, 1H), 3.58 (s, 3H), 1.43 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 177.4, 138.2, 135.1, 130.4, 128.2, 122.2, 116.1, 49.8, 48.3, 29.7, 21.4; IR (neat film, cm−1): 2918, 1697, 1648, 1541, 1514, 1459, 669; HRMS m/z (ESI) calcd for C11H10NOCl3+ [M+], 276.983 2; found, 276.982 2. 7-Chloro-3-(chloromethyl)-5-fluoro-1,3-dimethylindolin-2-one (2b). The product was isolated via the general procedure as a white solid in 48% yield (25.2 mg); flash chromatography (petroleum ether/ethyl acetate, 10:1); mp 53−55 °C; 1H NMR (400 MHz, CDCl3) δ 7.02−6.97 (m, 2H), 3.79 (d, J = 11.0 Hz, 1H), 3.70 (d, J = 10.9 Hz, 1H), 3.58 (s, 3H), 1.43 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 177.7, 159.6, 157.2, 135.7, 135.3, 135.2, 117.6, 117.3, 115.8, 115.7, 110.3, 110.0, 50.0, 48.5, 29.7, 21.4; IR (neat film, cm−1) 2922, 1699, 1652, 1539, 1514, 1456, 1336, 676; HRMS m/z (ESI) calcd for C11H10NOCl2F+ [M+], 261.011 9; found, 261.011 8. 5-Bromo-7-chloro-3-(chloromethyl)-1,3-dimethylindolin-2-one (2c). The product was isolated via the general procedure as a light-yellow oil in 69% yield (44 mg); preparative TLC (petroleum ether/ethyl acetate, 5:1); 1H NMR (400 MHz, CDCl3) δ 7.41 (s, 1H), 7.29 (s, 1H), 3.74 (dd, J = 38.5, 10.9 Hz, 2H), 3.57 (s, 3H), 1.42 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 177.4, 138.8, 135.6, 133.2, 125.0, 124.7, 115.2, 49.7, 48.4, 29.7, 21.5; IR (neat film, cm−1) 2920, 1706, 1649, 1536, 1509, 1456, 756, 673; HRMS m/z (ESI) calcd for C11H10NOCl2Br+ [M+], 320.931 8; found, 320.931 7. 7-Chloro-3-(chloromethyl)-5-iodo-1,3-dimethylindolin-2-one (2d). The product was isolated via the general procedure as a lightyellow oil in 43% yield (31.8 mg); preparative TLC (petroleum ether/ DCM = 1:1); 1H NMR (400 MHz, CDCl3) δ 7.59 (d, J = 1.6 Hz, 1H), 7.44 (d, J = 1.6 Hz, 1H), 3.79 (d, J = 10.8 Hz, 1H), 3.68 (d, J = 10.8 Hz, 1H), 3.58 (s, 3H), 1.42 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 167.1, 143.2, 138.9, 138.6, 130.4, 116.7, 93.8, 49.5, 48.4, 29.7, 21.5; IR (neat film, cm−1) 2922, 1704, 1645, 1538, 1512, 1457, 755, 672; HRMS m/z (ESI) calcd for C11H10NOCl2I+ [M+], 368.918 4; found, 368.918 2. 7-Chloro-3-(chloromethyl)-1,3-dimethyl-2-oxoindoline-5-carbonitrile (2e). The product was isolated via the general procedure as a white solid in 52% yield (28 mg); preparative TLC (petroleum ether/ethyl acetate, 5:1); mp 132−133 °C; 1H NMR (400 MHz, CDCl3) δ 7.59 (s, 1H), 7.44 (s, 1H), 3.81 (d, J = 10.9 Hz, 1H), 3.72 (d, J = 11.0 Hz, 1H), 3.63 (s, 3H), 1.46 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 177.6, 143.7, 135.40, 134.8, 124.7, 117.6, 116.2, 106.9, 49.4, 48.0, 29.8, 21.3; IR (neat film, cm−1) 2921, 2225, 1704, 1651, 1542, 1515, 1462, 673; HRMS m/z (ESI) calcd for C12H10N2OCl2+ [M+], 268.015 3; found, 268.016 5. 3-(Chloromethyl)-1,3,5-trimethylindolin-2-one (2f). The product was isolated via the general procedure as a yellow oil in 55% yield (28.4 mg); flash chromatography (petroleum ether/ethyl acetate, 10:1); 1H NMR (400 MHz, CDCl3) δ 7.20 (d, J = 7.6 Hz, 2H), 3.79 (d, J = 10.8 Hz, 1H), 3.55 (d, J = 10.8 Hz, 1H), 3.29 (s, 3H), 2.39 (s, 3H), 1.63 (s, 3H); 13 C NMR (100 MHz, CDCl3) δ 167.2, 140.6, 138.5, 130.0, 129.8, 128.2, 66.5, 51.8, 41.8, 27.6, 21.1; IR (neat film, cm−1) 2918, 1699, 1649, 1539, 1513, 1456, 672; HRMS m/z (ESI) calcd for C12H13NOCl2+ [M+], 257.037 4; found, 257.036 9. 5-Chloro-3-(chloromethyl)-1-ethyl-3,6-dimethylindolin-2-one and 5-Chloro-3-(chloromethyl)-1-ethyl-3,4-dimethylindolin-2-one (2g + 2g′). The product was isolated via the general procedure as a yellow oil in 79% yield (43 mg); flash chromatography (petroleum ether/ethyl acetate, 10:1); 1H NMR (400 MHz, CDCl3) δ 7.32 (d, J = 8.3 Hz, 1H), 7.27 (s, 0.43H), 6.75 (s, 0.45H), 6.68 (d, J = 8.3 Hz, 1.02H), 4.01−3.91 (m, 2.21H), 3.89−3.75 (m, 2.18H), 3.75−3.62 (m, 2.15H), 2.40 (d, J = 4.9 Hz, 4.77H), 1.47 (s, 3H), 1.40 (s, 1.59H), 1.27−1.22 (m, 5.78H); 13C NMR (100 MHz, CDCl3) δ 177.1, 177.1, 141.7, 141.2, 136.4, 132.8, 130.5, 129.8, 129.1, 129.0, 127.8, 124.1, 110.8, 107.0, 51.3, 49.6, 48.7, 46.7, 34.9, 21.2, 20.7, 20.1, 15.4, 14.2, 12.6, 12.5; IR (neat film, cm−1) 2925, 1701, 1632, 1545, 1521, 1509, 1455, 681; HRMS m/z (ESI) calcd for C13H15NOCl2+ [M+], 271.053 1; found, 271.053 3. 8-Chloro-1-(chloromethyl)-1-methyl-5,6-dihydro-1H-pyrrolo[3,2,1-ij]quinolin-2(4H)-one (2h). The product was isolated via the general procedure as a yellow oil in 67% yield (36.2 mg); flash

as a versatile oxidant, and H2O as the solvent makes this new transformation sustainable and practical. Ongoing studies are focused on applying this reaction to more complex molecules as well as gaining detailed insights into the reaction mechanism.

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EXPERIMENTAL SECTION

General Methods. All reagents and solvents used were obtained commercially and used without further purification unless otherwise indicated. Column chromatography was carried out on silica gel. All products were characterized by 1H NMR and 13C NMR and further characterized by HRMS. 1H NMR spectra were recorded on a 400 MHz spectrometer in CDCl3, and 13C NMR spectra were recorded on a 100 MHz spectrometer in CDCl3 using TMS as the internal standard. Multiplicities are indicated as s (singlet), d (doublet), t (triplet), q (quintet), and m (multiplet), and coupling constants (J) are reported in hertz. HRMS was measured on an electrospray ionization (ESI) apparatus using time-of-flight (ToF) mass spectrometry. IR spectra were obtained via a neat film on a NaCl plate. Melting points were determined using a XT-4 apparatus and are uncorrected. Preparation of N-Arylacrylamides. N-Arylacrylamide substrates 1 and 4 were prepared according to the literature.10b,11b,18 Preparation of HClO. HClO was prepared according to known procedures17a,19 and stored in the dark at about 0 °C before use. Typical Experimental Procedure for the Chlorocarbocyclization of Alkenes. To a 25 mL Schlenk tube were added (NH4)2S2O8 (6.0 equiv), NH4Cl (3.0 equiv), N-arylacrylamide 1 (0.2 mmol), and H2O (1.0 mL). Then the tube was stirred at 60 °C for the indicated time until complete consumption of the starting material (as detected by TLC). After the reaction was finished, the reaction mixture was cooled to room temperature, and ethyl acetate (EtOAc, 20 mL) and water (10 mL) were added. The organic layer was separated, and the aqueous phase was extracted with ethyl acetate. The combined organic layers were washed with brine, dried over Na2SO4, filtered, and concentrated in vacuum. The desired product was obtained after purification by flash column chromatography (petroleum ether/ethyl acetate) or preparative TLC on silica (petroleum ether/ethyl acetate or petroleum ether/DCM). Typical Experimental Procedure for Bromo- and Iodocarbocyclization of Alkenes. To a 25 mL Schlenk tube were added N-arylacrylamide 1 (0.2 mmol), (NH4)2S2O8 (2.5 equiv), NH4X (X = Br, I) (2.5 equiv), and H2O (1.0 mL). Then the tube was stirred at 60 °C for the indicated time until complete consumption of the starting material (as detected by TLC). After the reaction was finished, ethyl acetate (EtOAc, 20 mL) was added, the reaction mixture was washed with sat. Na2S2O3 and brine, and the organic layers were dried over Na2SO4, filtered, and concentrated. The residue was purified by column chromatography (silica gel, petroleum ether/ethyl acetate) to afford the corresponding products. Experimental Procedure for Preliminary Mechanistic Studies with Cl2. To a 15 mL tube were added N-arylacrylamide 1a (0.2 mmol) and H2O (1.0 mL). Then the reaction tube was charged with chlorine gas (approximately 0.67 mmol/15 mL) and stirred at 60 °C for 48 h. After the reaction, the mixture was cooled to room temperature, and saturated aqueous NaCl (15 mL) and EtOAc (30 mL) were added. The organic phase was separated, dried over Na2SO4, filtered, and concentrated. The crude mixture was purified by flash column chromatography (petroleum ether/ethyl acetate, 10:1) to afford desired compound 2a (38.4 mg, 69%). 3-(Chloromethyl)-1,3-dimethylindolin-2-one (3). The product was isolated via the general procedure as a light-yellow solid in 40% yield (16.8 mg); flash chromatography (petroleum ether/ethyl acetate, 10:1); mp 41−42 °C; 1H NMR (400 MHz, CDCl3) δ 7.33 (t, J = 6.9 Hz, 2H), 7.11 (t, J = 7.4 Hz, 1H), 6.88 (d, J = 7.5 Hz, 1H), 3.82−3.75 (m, 2H), 3.24 (s, 3H), 1.45 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 177.7, 143.5, 131.4, 128.6, 123.1, 122.8, 108.2, 49.6, 48.9, 26.4, 21.2; IR (neat film, cm−1) 2919, 1700, 1652, 1540, 1515, 1456, 672; HRMS m/z (ESI) calcd for C11H12NOCl+ [M+], 209.060 2; found, 209.060 2. 5,7-Dichloro-3-(chloromethyl)-1,3-dimethylindolin-2-one (2a). The product was isolated via the general procedure as a light-yellow F

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(s, 3H), 1.47 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 177.1, 152.2, 137.4, 131.8, 113.2, 111.2, 108.4, 57.0, 49.6, 36.8, 26.5, 22.1; IR (neat film, cm−1) 2940, 1708, 1661, 1557, 1508, 1423, 1129, 675, 617; HRMS m/z (ESI) calcd for C12H13NO2Br2+ [M+], 360.931 2; found, 360.931 1. 5-Bromo-3-(bromomethyl)-1-ethyl-3,6-dimethylindolin-2-one and 5-Bromo-3-(bromomethyl)-1-ethyl-3,4-dimethylindolin-2-one (2q + 2q′). The product was isolated via the general procedure as a yellow oil in 75% yield (54.2 mg); flash chromatography (petroleum ether/ethyl acetate, 10:1); 1H NMR (400 MHz, CDCl3) δ 7.52 (d, J = 8.3 Hz, 0.88H), 7.42 (s, 0.94H), 6.77 (s, 1H), 6.63 (d, J = 8.3 Hz, 0.81H), 3.90−3.76 (m, 4H), 3.73−3.60 (m, 3H), 3.56 (d, J = 10.0 Hz, 1H), 2.42 (d, J = 8.6 Hz, 6H), 1.52 (s, 3H), 1.44 (s, 3H), 1.27−1.23 (m, 6H); 13 C NMR (100 MHz, CDCl3) δ 177.1, 177.0, 142.2, 141.9, 138.2, 134.3, 132.3, 131.2, 130.4, 126.9, 117.5, 110.8, 107.6, 50.9, 49.0, 36.8, 34.9, 34.5, 29.7, 23.6, 22.2, 20.9, 18.3, 12.6, 12.5; HRMS m/z (ESI) calcd for C13H15NOBr2+ [M+], 358.951 0; found, 358.951 5. 5-Bromo-3-(bromomethyl)-1-ethyl-3,6-dimethylindolin-2-one (2q). Light-yellow solid (20.9 mg, 29%); mp 45−46 °C; 1H NMR (400 MHz, CDCl3) δ 7.42 (s, 1H), 6.77 (s, 1H), 3.83 (td, J = 7.2 Hz, 6.8 Hz, 6.4 Hz 1H), 3.72−3.63 (m, 2H), 3.56 (d, J = 10.0 Hz, 1H), 2.44 (s, 3H), 1.45 (s, 3H), 1.26 (t, J = 6.0 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 177.0, 141.9, 138.2, 131.2, 126.9, 117.5, 110.8, 49.0, 36.8, 34.9, 23.6, 22.2, 12.6; IR (neat film, cm−1) 2933, 1704, 1664, 1539, 1514, 1459, 1253, 1138, 680, 629; HRMS m/z (ESI) calcd for C13H15NOBr2+ [M+], 358.951 0; found, 358.951 5. 5-Iodo-3-(iodomethyl)-1,3-dimethylindolin-2-one (2r).11a The product was isolated via the general procedure as a white solid in 75% yield (64 mg); flash chromatography (petroleum ether/ethyl acetate, 10:1); mp 129−131 °C; 1H NMR (400 MHz, CDCl3) δ 7.65 (d, J = 8.1 Hz, 1H), 7.54 (s, 1H), 6.66 (d, J = 8.1 Hz, 1H), 3.50 (d, J = 9.8 Hz, 1H), 3.37 (d, J = 9.8 Hz, 1H), 3.21 (s, 3H), 1.50 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 177.2, 143.0, 137.5, 135.0, 131.5, 110.4, 85.2, 48.7, 26.4, 23.0, 9.9; IR (neat film, cm−1) 2925, 1706, 1648, 1539, 1516, 1459, 673, 529; HRMS m/z (ESI) calcd for C11H11NOI2+ [M+], 426.893 0; found, 426.893 2. 5-Chloro-3-(iodomethyl)-1,3-dimethylindolin-2-one (2s). The product was isolated via the general procedure as a white solid in 48% yield (32.2 mg); flash chromatography (petroleum ether/ethyl acetate, 10:1); mp 79−81 °C; 1H NMR (400 MHz, CDCl3) δ 7.31 (d, J = 8.3 Hz, 1H), 7.25 (d, J = 4.9 Hz, 1H), 6.80 (d, J = 8.2 Hz, 1H), 3.51 (d, J = 9.8 Hz, 1H), 3.38 (d, J = 9.8 Hz, 1H), 3.23 (s, 3H), 1.51 (s, 3H); 13 C NMR (100 MHz, CDCl3) δ 177.5, 141.8, 134.3, 128.6, 128.2, 123.3, 109.3, 48.9, 26.5, 23.0, 9.9; IR (neat film, cm−1) 2919, 1703, 1649, 1541, 1510, 1425, 668, 536; HRMS m/z (ESI) calcd for C11H11NOClI+ [M+], 334.956 1; found, 334.956 8. 3-(Iodomethyl)-5-methoxy-1,3-dimethylindolin-2-one (2t).11a The product was isolated via the general procedure as a light-yellow solid in 70% yield (46.3 mg); flash chromatography (petroleum ether/ ethyl acetate, 5:1); mp 94−95 °C; 1H NMR (400 MHz, CDCl3) δ 6.89 (d, J = 2.4 Hz, 1H), 6.85 (dd, J = 8.4, 2.5 Hz, 1H), 6.78 (d, J = 8.4 Hz, 1H), 3.81 (s, 3H), 3.45 (dd, J = 43.7, 9.8 Hz, 2H), 3.22 (s, 3H), 1.50 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 177.5, 156.0, 136.6, 133.9, 112.5, 110.3, 108.5, 55.8, 49.0, 26.4, 23.0, 10.8; IR (neat film, cm−1) 2932, 1701, 1662, 1559, 1511, 1426, 1125, 676, 541; HRMS m/z (ESI) calcd for C12H14NO2I+ [M+], 331.006 9; found, 331.007 1. 1-Ethyl-5-iodo-3-(iodomethyl)-3,6-dimethylindolin-2-one and 1Ethyl-5-iodo-3-(iodomethyl)-3,4-dimethylindolin-2-one (2u + 2u′). The product was isolated via the general procedure as a yellow oil in 88% yield (80 mg); flash chromatography (petroleum ether/ethyl acetate, 10:1); 1H NMR (400 MHz, CDCl3) δ 7.78 (d, J = 8.2 Hz, 0.49H), 7.61 (s, 1H), 6.79 (s, 1.06H), 6.50 (d, J = 8.2 Hz, 0.5H), 3.90−3.76 (m, 1.72H), 3.69−3.54 (m, 2.79H), 3.48 (d, J = 9.8 Hz, 1.1H), 3.34 (d, J = 9.8 Hz, 1.07H), 2.45 (s, 3.42H), 2.40 (s, 1.65H), 1.55 (s, 1.67H), 1.46 (s, 3.34H), 1.27−1.22 (m, 5.87H); 13C NMR (100 MHz, CDCl3) δ 177.2, 171.1, 142.9, 142.8, 141.7, 139.0, 137.3, 132.8, 132.4, 131.1, 110.0, 108.3, 94.6, 91.7, 50.5, 48.2, 35.0, 34.9, 28.8, 23.6, 23.0, 21.2, 12.7, 12.6, 10.3, 8.1; HRMS m/z (ESI) calcd for C13H15NOI2+ [M+], 454.924 1; found, 454.923 8. 1-Ethyl-5-iodo-3-(iodomethyl)-3,6-dimethylindolin-2-one (2u). Yellow solid (40.88 mg, 45%); mp 62−63 °C; 1H NMR (400 MHz, CDCl3) δ 7.62 (s, 1H), 6.80 (s, 1H), 3.88−3.79 (m, 1H), 3.73−3.61

chromatography (petroleum ether/ethyl acetate, 10:1); 1H NMR (400 MHz, CDCl3) δ 7.14 (s, 1H), 7.07 (s, 1H), 3.78−3.67 (m, 4H), 2.77 (t, J = 5.7 Hz, 2H), 2.00 (t, J = 5.8 Hz, 2H), 1.45 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 176.0, 137.8, 131.3, 127.6, 127.5, 121.7, 121.6, 51.1, 48.6, 38.9, 24.4, 21.0, 20.8; IR (neat film, cm−1) 1700, 1652, 1539, 1514, 1455, 671; HRMS m/z (ESI) calcd for C13H13NOCl2+ [M+], 269.036 8; found, 269.036 9. 5-Chloro-3-(chloromethyl)-3-(hydroxymethyl)-1-methylindolin2-one (2j). The product was isolated via the general procedure as a yellow oil in 73% yield (38 mg); flash chromatography (petroleum ether/ethyl acetate, 5:1); 1H NMR (400 MHz, CDCl3) δ 7.38−7.33 (m, 2H), 6.83 (d, J = 8.3 Hz, 1H), 4.01−3.81 (m, 4H), 3.23 (s, 3H), 2.08 (bs, 1H); 13C NMR (100 MHz, CDCl3) δ 176.1, 142.6, 129.3, 129.1, 128.5, 124.5, 109.4, 64.7, 55.2, 44.9, 26.5; IR (neat film, cm−1) 3625, 2924, 1699, 1652, 1539, 1513, 1457, 1150, 1061, 677; HRMS m/z (ESI) calcd for C11H11NO2Cl2+ [M+], 259.016 7; found, 259.016 5. (5-Chloro-3-(chloromethyl)-1-methyl-2-oxoindolin-3-yl)methyl Acetate (2k). The product was isolated via the general procedure as a yellow oil in 36% yield (21.7 mg); flash chromatography (petroleum ether/ethyl acetate, 10:1); 1H NMR (400 MHz, CDCl3) δ 7.36−7.34 (m, 2H), 6.82 (d, J = 8.0 Hz, 1H), 4.54 (d, J = 11.2 Hz, 1H), 4.24 (d, J = 11.2 Hz, 1H), 3.92 (d, J = 11.1 Hz, 1H), 3.82 (d, J = 11.1 Hz, 1H), 3.24 (s, 3H), 1.99 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 174.1, 170.1, 142.6, 129.3, 128.8, 128.3, 124.7, 109.3, 65.0, 53.4, 45.0, 26.6, 20.6; IR (neat film, cm−1) 2928, 1702, 1651, 1608, 1540, 1511, 1139, 1049, 675; HRMS m/z (ESI) calcd for C13H13NO3Cl2+ [M+], 301.027 2; found, 301.027 5. 5,7-Dichloro-3-(1-chloroethyl)-1,3-dimethylindolin-2-one (2l). The product was isolated via the general procedure as a yellow oil in 61% yield (35.6 mg); flash chromatography (petroleum ether/ethyl acetate, 10:1); 1H NMR (400 MHz, CDCl3) δ 7.43 (s, 1H), 7.27 (d, J = 5.3 Hz, 1H), 4.36 (q, J = 6.2 Hz, 1H), 3.56 (s, 3H), 1.51 (s, 3H), 1.21 (d, J = 6.4 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 177.7, 138.1, 134,5, 130.3, 128.3, 123.5, 115.9, 62.1, 53.1, 29.7, 22.9, 20.4; IR (neat film, cm−1) 2922, 1693, 1649, 1558, 1540, 1506, 1456, 681; HRMS m/z (ESI) calcd for C12H12NOCl3+ [M+], 290.997 0; found, 290.997 9. 5-Bromo-3-(bromomethyl)-1,3-dimethylindolin-2-one (2m).11b The product was isolated via the general procedure as a light-brown solid in 82% yield (54.6 mg); flash chromatography (petroleum ether/ ethyl acetate, 10:1); mp 89−90 °C; 1H NMR (400 MHz, CDCl3) δ 7.46−7.42 (m, 2H), 6.75 (d, J = 8.1 Hz, 1H), 3.62 (dd, J = 32.9, 10.0 Hz, 2H), 3.22 (s, 3H), 1.47 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 177.1, 142.4, 133.7,131.5, 126.2, 115.4, 109.7, 49.3, 36.4, 26.4, 22.1; IR (neat film, cm−1) 2923, 1713, 1652, 1539, 1514, 1456, 672, 623; HRMS m/z (ESI) calcd for C11H11NOBr2+ [M+], 330.920 7; found, 330.921 0. 7-Bromo-3-(bromomethyl)-5-chloro-1,3-dimethylindolin-2-one (2n). The product was isolated via the general procedure as a lightyellow solid in 59% yield (43.3 mg); flash chromatography (petroleum ether/ethyl acetate, 10:1); mp 98−101 °C; 1H NMR (400 MHz, CDCl3) δ 7.45 (s, 1H), 7.19 (s, 1H), 3.67 (d, J = 10.2 Hz, 1H), 3.59 (s, 3H), 3.53 (d, J = 10.2 Hz, 1H), 1.46 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 177.7, 139.6, 135.9, 133.5, 128.5, 122.5, 102.7, 49.2, 36.2, 30.0, 22.5; IR (neat film, cm−1) 2926, 1701, 1655, 1539, 1514, 1456, 672, 619; HRMS m/z (ESI) calcd for C11H10NOClBr2+ [M+], 364.882 2; found, 364.881 2. 7-Bromo-3-(bromomethyl)-5-iodo-1,3-dimethylindolin-2-one (2o). The product was isolated via the general procedure as a yellow solid in 67% yield (61.5 mg); flash chromatography (petroleum ether/ ethyl acetate, 10:1); mp 135−136 °C; 1H NMR (400 MHz, CDCl3) δ 7.59 (s, 1H), 7.31 (s, 1H), 3.67 (d, J = 10.1 Hz, 1H), 3.59 (s, 3H), 3.53 (d, J = 10.1 Hz, 1H), 1.46 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 177.6, 140.1, 136.6, 136.2, 125.2, 115.6, 103.1, 49.2, 36.2, 30.0, 22.5; IR (neat film, cm−1) 2923, 1698, 1651, 1538, 1515 1455, 673, 613, 517; HRMS m/z (ESI) calcd for C11H10NOBr2I+ [M+], 456.816 9; found, 456.817 1. 6-Bromo-3-(bromomethyl)-5-methoxy-1,3-dimethylindolin-2one (2p).11b The product was isolated via the general procedure as a brown solid in 92% yield (66.8 mg); flash chromatography (petroleum ether/ethyl acetate, 5:1); mp 66−67 °C; 1H NMR (400 MHz, CDCl3) δ 7.07 (s, 1H), 6.95 (s, 1H), 3.90 (s, 3H), 3.62 (q, J = 10.1 Hz, 2H), 3.19 G

dx.doi.org/10.1021/jo501741w | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry

Article

(m, 1H), 3.50 (d, J = 9.8 Hz, 1H), 3.35 (d, J = 9.8 Hz, 1H), 2.47 (s, 3H), 1.48 (s, 3H), 1.27 (t, J = 7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 177.2, 142.8, 141.7, 132.8, 132.4, 110.0, 91.6, 48.2, 34.9, 28.8, 23.0, 12.7, 10.2; IR (neat film, cm−1) 2929, 1699, 1658, 1539, 1515, 1455, 1261, 1127, 674, 543; HRMS m/z (ESI) calcd for C13H15NOI2+ [M+], 454.924 1; found, 454.923 8. 2,3-Dichloro-N-(2,6-dimethylphenyl)-N,2-dimethylpropanamide and 3-Chloro-N-(2,6-dimethylphenyl)-2-hydroxy-N,2-dimethylpropanamide (5 + 6). Yellow oil (23.8 mg, 45%); 1H NMR (400 MHz, CDCl3) δ 7.19−7.07 (m, 4.59H), 4.37 (d, J = 10.2 Hz, 0.96H), 4.19 (d, J = 11.7 Hz, 0.54H), 3.99 (d, J = 11.7 Hz, 0.53H), 3.63 (d, J = 10.2 Hz, 1H), 3.51 (s, 1.58H), 3.21 (s, 3H), 2.35 (s, 3H), 2.28 (s, 3H), 2.21 (s, 1.64H), 2.17 (s, 1.57H), 2.03 (s, 1.68H), 1.77 (bs, 0.59), 1.33 (s, 3H); 13 C NMR (101 MHz, CDCl3) δ 167.4, 166.9, 142.0, 141.3, 136.3, 135.9, 134.6, 134.3, 128.9, 128.8, 128.7, 128.6, 128.5, 127.7, 67.6, 66.7, 53.7, 52.1, 38.8, 38.3, 26.3, 26.1, 18.3, 18.1, 17.4, 17.2; LRMS m/z calcd for C13H17Cl2NO [M + H], 273; found, 273; LRMS m/z calcd for C13H18ClNO2 [M + H], 255; found, 255.

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(4) (a) Xie, J.; Xu, P.; Li, H.-M.; Xue, Q.-C.; Jin, H.-M.; Cheng, Y.-X.; Zhu, C.-J. Chem. Commun. 2013, 49, 5672. (b) Xu, P.; Xie, J.; Xue, Q.-C.; Pan, C.-D.; Cheng, Y.-X.; Zhu, C.-J. Chem.Eur. J. 2013, 19, 14039. (5) Jaegli, S.; Dufour, J.; Wei, H.-L.; Piou, T.; Duan, X.-H.; Vors, J.-P.; Neuville, L.; Zhu, J.-P. Org. Lett. 2010, 12, 4498. (6) (a) Wei, X.-H.; Li, Y.-M.; Zhou, A.-X.; Yang, T.-T.; Yang, S.-D. Org. Lett. 2013, 15, 4158. (b) Matcha, K.; Narayan, R.; Antonchick, A. P. Angew. Chem., Int. Ed. 2013, 52, 7985. (7) (a) Li, Y.-M.; Sun, M.; Wang, H.-L.; Tian, Q.-P.; Yang, S.-D. Angew. Chem., Int. Ed. 2013, 52, 3972. (b) Li, Y.-M.; Shen, Y.-H.; Chang, K.-J.; Yang, S.-D. Tetrahedron. 2014, 70, 1991. (8) (a) Li, X.-Q.; Xu, X.-S.; Hu, P.-Z.; Xiao, X.-Q.; Zhou, C. J. Org. Chem. 2013, 78, 7343. (b) Liu, J.-D.; Zhuang, S.-B.; Gui, Q.-W.; Chen, X.; Yang, Z.-Y.; Tan, Z. Eur. J. Org. Chem. 2014, 3196. (9) Yin, F.; Wang, X.-S. Org. Lett. 2014, 16, 1128. (10) For selected examples, see (a) Li, L.; Deng, M.; Zheng, S.-C.; Xiong, Y.-P.; Tan, B.; Liu, X.-Y. Org. Lett. 2014, 16, 504. (b) Mu, X.; Wu, T.; Wang, H.-Y.; Guo, Y.-L.; Liu, G.-S. J. Am. Chem. Soc. 2012, 134, 878. (c) Kong, W.; Casimiro, M.; Merino, E.; Nevado, C. J. Am. Chem. Soc. 2013, 135, 14480. (d) Kong, W. Q.; Casimiro, M.; Fuentes, N.; Merino, E.; Nevado, C. Angew. Chem., Int. Ed. 2013, 52, 13324. (11) For iodo- and bromocarbocyclization of alkenes to access oxindoles, see (a) Wei, H.-L.; Piou, T.; Dufour, J.; Neuville, L.; Zhu, J. P. Org. Lett. 2011, 13, 2244. (b) Fabry, D. C.; Stodulski, M.; Hoerner, S.; Gulder, T. Chem.Eur. J. 2012, 18, 10834. (12) (a) Wei, W.; Wen, J. W.; Yang, D. S.; Du, J.; Wang, H. Green Chem. 2014, 16, 2988. (b) Jing, C. C.; Shi, T. D.; Xing, D.; Guo, X.; Hu, W.-H. Green Chem. 2013, 15, 620. (c) Nematollahi, D.; Mirahmadpour, P. Sustainable Chem. Eng. 2014, 2, 579. (13) For the latest examples of the synthesis of oxindoles, see (a) Shen, T.; Yuan, Y. Z.; Jiao, N. Chem. Commun. 2014, 50, 554. (b) Fu, W.-J.; Xu, F.-J.; Fu, Y.-Q.; Xu, C.; Li, S.-H.; Zou, D.-P. Eur. J. Org. Chem. 2014, 709. (c) Wei, W.; Wen, J.-W.; Yang, D.-S.; Liu, X.-X.; Guo, M.-Y.; Dong, R.M.; Wang, H. J. Org. Chem. 2014, 79, 4225. (d) Lv, J. L.; Negrerie, D. Z.; Deng, J.; Du, Y. F.; Zhao, K. J. Org. Chem. 2014, 79, 1111. (14) Yang, F.; Klumphu, P.; Liang, Y.-M.; Lipshutz, B. H. Chem. Commun. 2014, 50, 936. (15) The chlorination of the aromatic ring was not observed in the presence of TEMPO; the detrimental effect of TEMPO could result from its inhibiting effect on the formation of the electrophilic chlorination species. For selected examples, see Bjørsvik, H.-R.; Liguori, L.; Minisci, F. Org. Process Res. Dev. 2002, 6, 197. (16) The formation of molecular iodine can be seen clearly in Figure S1. To confirm this further, we used 2.5 equiv of I2; the reaction also occurred in water with a 38% isolated yield of 2r. (17) (a) Marmor, S.; Maroski, J. G. J. Org. Chem. 1966, 31, 4278. (b) Narender, N.; Srinivasu, P.; Kulkarni, S. J.; Raghavan, K. V. Synth. Commun. 2002, 32, 279. (c) Swain, C. G.; Crist, D. L. R. J. Am. Chem. Soc. 1972, 94, 3195. (18) Pinto, A.; Jia, Y.; Neuville, L.; Zhu, J. Chem.−Eur.J 2007, 13, 961. (19) Chung, A.; Israel, G. C. J. Chem. Soc. 1955, 2667.

ASSOCIATED CONTENT

S Supporting Information *

Copies of 1H and 13C spectra for all products, solubility experiment data, and halogen formation pictures. This material is available free of charge via the Internet at http://pubs.acs.org.

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AUTHOR INFORMATION

Corresponding Author

*E-mail: [email protected]. Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS

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REFERENCES

We are grateful for financial support from the National Natural Science Foundation of China (no. 21372068).

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dx.doi.org/10.1021/jo501741w | J. Org. Chem. XXXX, XXX, XXX−XXX